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  • 1
    Online Resource
    Online Resource
    Trans Tech Publications, Ltd. ; 2017
    In:  Materials Science Forum Vol. 892 ( 2017-3), p. 10-15
    In: Materials Science Forum, Trans Tech Publications, Ltd., Vol. 892 ( 2017-3), p. 10-15
    Abstract: This paper examines the economic costs and benefits of the use of an ultrasonic wire or tape cleaning system. In the last years, major technology improvements made the use of power ultrasound more reasonable for the cleaning of wires. The cavitation of modern high-power ultrasonic processors serves to remove grease, oil, and other contaminations from the surface of the wire. Reduced investment costs and high performance of these ultrasonic wire cleaning systems made them not only competitive but superior to conventional cleaning methods as for example acid baths.
    Type of Medium: Online Resource
    ISSN: 1662-9752
    URL: Issue
    Language: Unknown
    Publisher: Trans Tech Publications, Ltd.
    Publication Date: 2017
    detail.hit.zdb_id: 2047372-2
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  • 2
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 25, No. Supplement_1 ( 2023-06-12), p. i55-i55
    Abstract: Pediatric low-grade gliomas (pLGG), the most common brain tumors in children, are driven by alterations in the MAPK pathway. Several clinical trials have shown the potential for MAPK inhibitors (MAPKi) treatment in pLGG. However, the range of response is broad, even within entities sharing the same driving genetic MAPK alteration. A predictive stratification tool is needed to identify patients that will be more likely to benefit from MAPKi therapy. METHODS We generated gene-expression-based MAPKi sensitivity scores (MSS) for each MAPKi class (BRAFi, MEKi, ERKi), based on MAPK-related genes differentially regulated between MAPKi sensitive and non-sensitive cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset. Single sample Gene Set Enrichment Analysis (ssGSEA) was used to measure and validate our MSSs in the GDSC dataset and an independent PDX dataset (XevaDB). The validated signatures were tested in a pLGG-specific background, using gene expression data from PA cell lines and primary pLGG samples. RESULTS Our MSS could differentiate MAPKi sensitive cells in the GDSC dataset, and significantly correlated with MAPKi response in the XevaDB PDX dataset. The MSS were able to differentiate glioma entities with differing MAPK alterations from non-MAPK altered entities, and showed the highest scores in pLGG. The MSSs were heterogeneous within pLGG entities with a common MAPK alteration, as observed in MAPKi clinical studies. Intriguingly, a strong correlation between our MSS and the predicted immune cell infiltration rate, as determined by the Estimate score, was observed and confirmed in a pLGG scRNA sequencing dataset. CONCLUSION These data demonstrate the relevance of gene-expression signatures to predict response to MAPKi treatment in pLGG, and will be further investigated in a prospective manner in upcoming clinical trials. In addition, our data could suggest a role of immune infiltration in the response to MAPKi in pLGG that warrants further validation.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2094060-9
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  • 3
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-07-27)
    Abstract: Pediatric low-grade gliomas (pLGG) show heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. Thus, more complex stratification biomarkers are needed to identify patients likely to benefit from MAPKi therapy. Here, we identify MAPK-related genes enriched in MAPKi-sensitive cell lines using the GDSC dataset and apply them to calculate class-specific MAPKi sensitivity scores (MSSs) via single-sample gene set enrichment analysis. The MSSs discriminate MAPKi-sensitive and non-sensitive cells in the GDSC dataset and significantly correlate with response to MAPKi in an independent PDX dataset. The MSSs discern gliomas with varying MAPK alterations and are higher in pLGG compared to other pediatric CNS tumors. Heterogenous MSSs within pLGGs with the same MAPK alteration identify proportions of potentially sensitive patients. The MEKi MSS predicts treatment response in a small set of pLGG patients treated with trametinib. High MSSs correlate with a higher immune cell infiltration, with high expression in the microglia compartment in single-cell RNA sequencing data, while low MSSs correlate with low immune infiltration and increased neuronal score. The MSSs represent predictive tools for the stratification of pLGG patients and should be prospectively validated in clinical trials. Our data supports a role for microglia in the response to MAPKi.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2553671-0
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  • 4
    In: The Lancet Oncology, Elsevier BV, Vol. 21, No. 5 ( 2020-05), p. 699-709
    Type of Medium: Online Resource
    ISSN: 1470-2045
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2049730-1
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  • 5
    In: Investigative Radiology, Ovid Technologies (Wolters Kluwer Health), Vol. 58, No. 4 ( 2023-4), p. 273-282
    Abstract: Diffusion-weighted magnetic resonance imaging (MRI) is increasingly important in patients with multiple myeloma (MM). The objective of this study was to train and test an algorithm for automatic pelvic bone marrow analysis from whole-body apparent diffusion coefficient (ADC) maps in patients with MM, which automatically segments pelvic bones and subsequently extracts objective, representative ADC measurements from each bone. Materials and Methods In this retrospective multicentric study, 180 MRIs from 54 patients were annotated (semi)manually and used to train an nnU-Net for automatic, individual segmentation of the right hip bone, the left hip bone, and the sacral bone. The quality of the automatic segmentation was evaluated on 15 manually segmented whole-body MRIs from 3 centers using the dice score. In 3 independent test sets from 3 centers, which comprised a total of 312 whole-body MRIs, agreement between automatically extracted mean ADC values from the nnU-Net segmentation and manual ADC measurements from 2 independent radiologists was evaluated. Bland-Altman plots were constructed, and absolute bias, relative bias to mean, limits of agreement, and coefficients of variation were calculated. In 56 patients with newly diagnosed MM who had undergone bone marrow biopsy, ADC measurements were correlated with biopsy results using Spearman correlation. Results The ADC-nnU-Net achieved automatic segmentations with mean dice scores of 0.92, 0.93, and 0.85 for the right pelvis, the left pelvis, and the sacral bone, whereas the interrater experiment gave mean dice scores of 0.86, 0.86, and 0.77, respectively. The agreement between radiologists' manual ADC measurements and automatic ADC measurements was as follows: the bias between the first reader and the automatic approach was 49 × 10 −6 mm 2 /s, 7 × 10 −6 mm 2 /s, and −58 × 10 −6 mm 2 /s, and the bias between the second reader and the automatic approach was 12 × 10 −6 mm 2 /s, 2 × 10 −6 mm 2 /s, and −66 × 10 −6 mm 2 /s for the right pelvis, the left pelvis, and the sacral bone, respectively. The bias between reader 1 and reader 2 was 40 × 10 −6 mm 2 /s, 8 × 10 −6 mm 2 /s, and 7 × 10 −6 mm 2 /s, and the mean absolute difference between manual readers was 84 × 10 −6 mm 2 /s, 65 × 10 −6 mm 2 /s, and 75 × 10 −6 mm 2 /s. Automatically extracted ADC values significantly correlated with bone marrow plasma cell infiltration ( R = 0.36, P = 0.007). Conclusions In this study, a nnU-Net was trained that can automatically segment pelvic bone marrow from whole-body ADC maps in multicentric data sets with a quality comparable to manual segmentations. This approach allows automatic, objective bone marrow ADC measurements, which agree well with manual ADC measurements and can help to overcome interrater variability or nonrepresentative measurements. Automatically extracted ADC values significantly correlate with bone marrow plasma cell infiltration and might be of value for automatic staging, risk stratification, or therapy response assessment.
    Type of Medium: Online Resource
    ISSN: 1536-0210 , 0020-9996
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2041543-6
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  • 6
    In: Investigative Radiology, Ovid Technologies (Wolters Kluwer Health), Vol. 57, No. 9 ( 2022-9), p. 601-612
    Abstract: The aim of this study was to estimate the prospective utility of a previously retrospectively validated convolutional neural network (CNN) for prostate cancer (PC) detection on prostate magnetic resonance imaging (MRI). Materials and Methods The biparametric (T2-weighted and diffusion-weighted) portion of clinical multiparametric prostate MRI from consecutive men included between November 2019 and September 2020 was fully automatically and individually analyzed by a CNN briefly after image acquisition (pseudoprospective design). Radiology residents performed 2 research Prostate Imaging Reporting and Data System (PI-RADS) assessments of the multiparametric dataset independent from clinical reporting (paraclinical design) before and after review of the CNN results and completed a survey. Presence of clinically significant PC was determined by the presence of an International Society of Urological Pathology grade 2 or higher PC on combined targeted and extended systematic transperineal MRI/transrectal ultrasound fusion biopsy. Sensitivities and specificities on a patient and prostate sextant basis were compared using the McNemar test and compared with the receiver operating characteristic (ROC) curve of CNN. Survey results were summarized as absolute counts and percentages. Results A total of 201 men were included. The CNN achieved an ROC area under the curve of 0.77 on a patient basis. Using PI-RADS ≥3-emulating probability threshold (c3), CNN had a patient-based sensitivity of 81.8% and specificity of 54.8%, not statistically different from the current clinical routine PI-RADS ≥4 assessment at 90.9% and 54.8%, respectively ( P = 0.30/ P = 1.0). In general, residents achieved similar sensitivity and specificity before and after CNN review. On a prostate sextant basis, clinical assessment possessed the highest ROC area under the curve of 0.82, higher than CNN (AUC = 0.76, P = 0.21) and significantly higher than resident performance before and after CNN review (AUC = 0.76 / 0.76, P ≤ 0.03). The resident survey indicated CNN to be helpful and clinically useful. Conclusions Pseudoprospective paraclinical integration of fully automated CNN-based detection of suspicious lesions on prostate multiparametric MRI was demonstrated and showed good acceptance among residents, whereas no significant improvement in resident performance was found. General CNN performance was preserved despite an observed shift in CNN calibration, identifying the requirement for continuous quality control and recalibration.
    Type of Medium: Online Resource
    ISSN: 1536-0210 , 0020-9996
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2041543-6
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  • 7
    In: Investigative Radiology, Ovid Technologies (Wolters Kluwer Health), Vol. 57, No. 11 ( 2022-11), p. 752-763
    Abstract: Disseminated bone marrow (BM) involvement is frequent in multiple myeloma (MM). Whole-body magnetic resonance imaging (wb-MRI) enables to evaluate the whole BM. Reading of such whole-body scans is time-consuming, and yet radiologists can transfer only a small fraction of the information of the imaging data set to the report. This limits the influence that imaging can have on clinical decision-making and in research toward precision oncology. The objective of this feasibility study was to implement a concept for automatic, comprehensive characterization of the BM from wb-MRI, by automatic BM segmentation and subsequent radiomics analysis of 30 different BM spaces (BMS). Materials and Methods This retrospective multicentric pilot study used a total of 106 wb-MRI from 102 patients with (smoldering) MM from 8 centers. Fifty wb-MRI from center 1 were used for training of segmentation algorithms (nnU-Nets) and radiomics algorithms. Fifty-six wb-MRI from 8 centers, acquired with a variety of different MRI scanners and protocols, were used for independent testing. Manual segmentations of 2700 BMS from 90 wb-MRI were performed for training and testing of the segmentation algorithms. For each BMS, 296 radiomics features were calculated individually. Dice score was used to assess similarity between automatic segmentations and manual reference segmentations. Results The “multilabel nnU-Net” segmentation algorithm, which performs segmentation of 30 BMS and labels them individually, reached mean dice scores of 0.88 ± 0.06/0.87 ± 0.06/0.83 ± 0.11 in independent test sets from center 1/center 2/center 3–8 (interrater variability between radiologists, 0.88 ± 0.01). The subset from the multicenter, multivendor test set (center 3–8) that was of high imaging quality was segmented with high precision (mean dice score, 0.87), comparable to the internal test data from center 1. The radiomic BM phenotype consisting of 8880 descriptive parameters per patient, which result from calculation of 296 radiomics features for each of the 30 BMS, was calculated for all patients. Exemplary cases demonstrated connections between typical BM patterns in MM and radiomic signatures of the respective BMS. In plausibility tests, predicted size and weight based on radiomics models of the radiomic BM phenotype significantly correlated with patients' actual size and weight ( P = 0.002 and P = 0.003, respectively). Conclusions This pilot study demonstrates the feasibility of automatic, objective, comprehensive BM characterization from wb-MRI in multicentric data sets. This concept allows the extraction of high-dimensional phenotypes to capture the complexity of disseminated BM disorders from imaging. Further studies need to assess the clinical potential of this method for automatic staging, therapy response assessment, or prediction of biopsy results.
    Type of Medium: Online Resource
    ISSN: 1536-0210 , 0020-9996
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2041543-6
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  • 8
    In: Leukemia, Springer Science and Business Media LLC, Vol. 34, No. 11 ( 2020-11), p. 3105-3105
    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Type of Medium: Online Resource
    ISSN: 0887-6924 , 1476-5551
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2008023-2
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  • 9
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1829-1829
    Abstract: Abstract 1829 Poster Board I-855 Introduction In addition to current clinical and cytogenetic risk factors, several highly predictive gene expression based risk stratifications have been proposed in multiple myeloma. At the same time, putative drugable targets have been identified which are only expressed in a subpopulation of myeloma patients (e.g. AURKA). Whereas assessment of both works well within a clinical trial or an experimental setting, they can currently not readily be applied to clinical routine. Methods As reference a group of 300 Affymetrix U133 Plus 2.0 DNA microarrays from patients with multiple myeloma is preprocessed using GC-RMA. Quality control of the DNA microarrays is implemented according to the MACQ-Project. Gene expression based prediction of sex, immunoglobulin- and light chain type is used as sample identity-test within a multicenter-setting. Gene expression based risk stratification (IFM-score, 70-gene high risk score, gene expression based proliferation index) and molecular classifications are assessed as published, as are individual target genes e.g. AURKA. To classify a patient within a prospective clinical routine setting, the documentation by value strategy (Kostka & Spang, 2008) was adapted for GC-RMA preprocessing and is used for documenting the quantitative preprocessing information of the reference group. The gene expression based report is developed in the open source language R, containing a GUI based on Gtk2, and the final report is created as a PDF-file. Results We present here our publicly available (http://code.google.com/p/gep-r) open source software-framework (GEP-R) that allows creating a gene expression based report from Affymetrix raw-data. The risk stratification of an individual patient is assessed and based on saved preprocessing information of a reference cohort by treating the individual patient's expression data as being part of this group, assuring comparable risk stratification. Results can be interpreted and commented within the report and a PDF based document be created. The generation of the report can be performed within short time on a standard computer. Conclusion Gene expression reporting allows validated assessment of risk and of individual therapeutic targets in myeloma patients within a clinical routine setting. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Zeitschrift für Gastroenterologie, Georg Thieme Verlag KG, Vol. 57, No. 09 ( 2019-09), p. 1051-1058
    Abstract: Background and aim Colorectal cancer (CRC) screening can effectively reduce cancer-associated mortality. In Germany, individuals over the age of 50 or 55 have access to CRC screening services. However, utilization rates are persistently low, particular in the male population. This observational study investigates the effect of standard versus gender-specific invitation letters on utilization of CRC screening services. Methods We analyzed utilization rates of individuals who were insured by a large health insurance fund in Bavaria, Germany. Persons who became eligible for CRC screening received a standard (2013–2014) or a gender-specific invitation letter (2015–2016). We compared utilization rates within 6 months after receipt of the invitation letter using billing codes of the health insurance fund. Results Invitation letters were sent to 49 535 individuals, of which 48.8 % were gender-specific. The overall utilization rate did not differ between recipients of the standard versus gender-specific invitation letter (11.6 % vs 11.1 %; RR: 0.97 [0.92–1.02], p = 0.19). However, uptake of screening colonoscopy was significantly higher among recipients of gender-specific invitations (2.9 % vs 3.5 %; RR: 1.21 [1.04–1.39] , p = 0.01), whereas utilization of fecal occult blood tests declined (10.4 % vs 9.7 %; RR: 0.93 [0.88–0.99], p = 0.016). Conclusions Gender-specific design of invitation letters can modify the patients’ preference for specific CRC screening services and increase the acceptance of screening colonoscopy.
    Type of Medium: Online Resource
    ISSN: 0044-2771 , 1439-7803
    RVK:
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2019
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